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Updated: Mar 6, 2026
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
Sfrp2 in Microglia Inhibited S100a8-Mediated Neuroinflammation and Protected Neural Damage Following Retinal
Shuya Tao1, Wen Hu2, Yaguang Hu3
1Zhongshan Ophthalmic Center, Sun Yat-Sen University, WHO Collaborating Centre for Eye Care and Vision, State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People's Republic of China.
Secreted frizzled-related protein 2 (Sfrp2) in microglia protects the retina from ischemia reperfusion (I/R) injury. Loss of Sfrp2 worsens neuroinflammation and vision loss in I/R models.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Retinal ischemia reperfusion (I/R) injury causes significant vision loss.
- Microglia play a critical role in retinal inflammation following I/R.
- The specific role of Sfrp2 in microglial response to I/R is not well understood.
Purpose of the Study:
- To investigate the expression and function of Sfrp2 in the retina during I/R.
- To elucidate the underlying mechanisms of Sfrp2's role in microglial-mediated inflammation.
- To explore Sfrp2 as a potential therapeutic target for ischemic retinopathy.
Main Methods:
- Established in vivo I/R mouse and in vitro lipopolysaccharide-stimulated BV2 cell models.
- Assessed Sfrp2 expression using immunohistochemistry and Western blotting.
- Utilized Cre-lox mediated deletion and siRNA to ablate microglial Sfrp2.
- Evaluated retinal structure, neuronal survival, apoptosis, and function via H&E, immunofluorescence, TUNEL, and electroretinography.
- Investigated mechanisms using RNA-sequencing, Western blotting, and immunoprecipitation.
Main Results:
- Sfrp2 expression was upregulated in the retina following I/R and localized to microglia.
- Microglial Sfrp2 deficiency aggravated retinal damage, neuronal loss, and visual dysfunction.
- Loss of Sfrp2 activated the TRAF6-TAK1-NF-κB pathway, increasing S100a8 expression.
- S100a8 inhibition partially rescued retinal injury in Sfrp2-deficient models.
Conclusions:
- Microglial Sfrp2 inhibits the TRAF6-TAK1-NF-κB signaling pathway and S100a8, reducing neuroinflammation.
- Sfrp2 acts protectively against retinal damage and vision loss in I/R.
- Sfrp2 represents a promising therapeutic target for ischemic retinopathy.
